The objective of this renewal proposal is to bring to completion a study, in the human subject, of the effects of aging on corticosteroid metabolism and production, primarily by the adrenal gland, and secondarily by the gonads. Our investigations have revealed that in men aging has caused a significant reduction in the adrenal and testicular secretion of four C-21 deoxycorticosteroids: pregnenolone, progesterone, 17-hydroxypregnenolone and 17 -dehydroxyprogesterone, and more recently, of pregnenolone sulfate in contrast to cortisol secretion which is relatively well maintained with advancing years. Administration of ACTH has revealed, furthermore, that the elderly adrenal gland retains the capacity to produce as much pregnenolone, pregnenolone sulfate, progesterone and cortisol as young subjects. Despite this potential capacity, aging apparently diminishes total adrenal steroid biosynthesis via the pathway pregnenolone yields cortisol at the expense of the less polar precursors. We are thus interested in determining the effects of aging on the 17- deoxycorticosteroid pathway to aldosterone, the secretion of which declines significantly with age (Tait et al.). However, during our current grant period, we will be unable either to complete our measurements of the secretion of corticosterone and desoxycorticosterone or to initiate our proposed study of the effect of aging on adrenal utilization of blood cholesterol for cortisol biosynthesis.